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Progression of obsessive compulsive disorder-like grooming in Sapap3 knockout mice: A longitudinal [11C]ABP688 PET study
- Source :
- Neuropharmacology
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- UNLABELLED: We aimed to evaluate [3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-0-11C-methyloxime] ([11C]ABP688) small animal positron emission tomography (μPET) as a biomarker to visualize possible longitudinal changes in metabotropic glutamate receptor 5 (mGluR5) availability in the brain of SAP90/PSD-95 associated protein 3 (Sapap3) knockout (ko) mice, showing obsessive compulsive disorder (OCD)-like behavior. METHODS: Alongside the assessment of grooming, we performed [11C]ABP688 μPET/CT imaging in wildtype (wt; n=10) and ko (n=11) mice both at 3 and 9 months. Using the simplified reference tissue method (SRTM), the nondisplaceable binding potential (BPND) was calculated representing the in vivo availability of the metabotropic glutamate receptor 5 (mGluR5) in the brain with the cerebellum as a reference region. Longitudinal voxel-based statistical parametric mapping (SPM) was performed on BPND images. Results were verified using [11C]ABP688 ex vivo autoradiography, [3H]ABP688 in vitro autoradiography, and mGluR5 immunohistochemistry. RESULTS: Cross-sectional comparisons revealed significantly increased grooming parameters in ko animals, at both time points. A significant longitudinal increase in % grooming duration (+268.25%; p
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Hippocampus
Striatum
Statistical parametric mapping
Amygdala
Mouse model
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
In vivo
Internal medicine
Medicine
Pharmacology
Obsessive compulsive disorder (OCD)
business.industry
Metabotropic glutamate receptor 5
Pharmacology. Therapy
Binding potential
Grooming behavior
SAP90/PSD-95 associated protein 3 (Sapap3)
Cortex (botany)
PET
030104 developmental biology
medicine.anatomical_structure
Endocrinology
nervous system
Metabotropic glutamate receptor 5 (mGluR5)
Human medicine
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....8dff1d3bef37df19da67653c06c362e1